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目的明确青海地区回族苯丙酮尿症患者苯丙氨酸羟化酶(PAH)基因的突变特征,为该地区苯丙酮尿症(PKU)的产前诊断和遗传咨询提供理论依据。方法应用PCR产物直接测序法对13例回族PKU患儿及其父母的PAH基因启动子、第1~13外显子及其旁侧内含子区域进行基因突变分析。结果在26个PAH等位基因中检测出15种不同的突变基因,总检测率为80.8%(21/26),包括10种错义突变(66.7%)、3种无义突变(20.0%)和2种剪切位点突变(13.3%),大部分突变集中在第3、6、7、11外显子及第4内含子区域,常见的4种突变是R243Q(15.4%)、IVS4-1 G>A(7.7%)、I65T(7.7%)、P281L(7.7%)。R243Q是青海地区回族PAH基因最常见的突变种类,P281L突变在宁夏及新疆回族中均未检出,可能是青海回族特有的热点突变。R53H、I65S、R158Q、V230I、R252Q和P281L这6种突变在中国回族人群中为首次报道。结论青海与宁夏、新疆回族在PAH基因的突变构成上差异显著,R243Q、IVS4-1 G>A、I65T、P281L可能属于青海回族PAH基因突变的热点。
Objective To determine the mutation of phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria in Qinghai and to provide theoretical basis for prenatal diagnosis and genetic counseling of phenylketonuria (PKU) in this area. Methods The gene mutations of PAH gene promoter, exons 1 to 13 and its intron regions in 13 PKU children and their parents were analyzed by PCR products. Results Fifteen different mutations were detected in 26 PAH alleles with a total detection rate of 80.8% (21/26) including 10 missense mutations (66.7%), 3 nonsense mutations (20.0%), (13.3%). Most of the mutations were concentrated in exon 3, 6, 7, 11 and intron 4. The four common mutations were R243Q (15.4%), IVS4 -1 G> A (7.7%), I65T (7.7%), P281L (7.7%). R243Q is the most common mutation of PAH gene from Hui in Qinghai. The P281L mutation was not detected in Ningxia and Hui in Xinjiang, which may be a unique hot mutation in Qinghai Hui. Six mutations of R53H, I65S, R158Q, V230I, R252Q and P281L were reported for the first time in Chinese Hui population. Conclusion There are significant differences in the PAH gene mutations among Qinghai, Ningxia and Xinjiang Hui people. R243Q, IVS4-1 G> A, I65T and P281L may be the hot spots of PAH gene mutation in Qinghai.